The mesodermal germ layer gives rise to a variety of functionally important cell types, including different muscle and non-muscle cells. Elucidating how different mesodermal cell fates are specified is not only important to the understanding of early stages of animal development, but will also guide investigations into the molecular basis of various cancers and genetic diseases that specifically affect mesodermally derived cell types. The long-term goal of this proposal is to understand the mechanisms required for mesodermal cell fate specification and diversification using the C. elegans postembryonic mesodermal lineage, the M lineage, as a model system. The M lineage is derived from a single precursor cell and produces a number of different muscle and non- muscle cell types. A number of key factors and pathways involved in M lineage fate specification have been identified, including SMA-9, the sole C. elegans homolog of the Drosophila and vertebrate Schnurri (SHN) proteins. Our analysis on SMA-9 function suggests that SMA-9 specifically antagonizes TGF_ signaling in the M lineage. Interestingly, SMA-9 also regulates body size, but by playing a contributory role in the TGF_ pathway. Thus SMA-9 exerts context-dependent activities in modulating the TGF_ pathway. In this proposal, Specific aims 1 and 2 are designed to identify SMA-9 cofactors and downstream targets that are mediating these context-dependent activities.
Specific aim 3 is designed to determine the functions of three genes that are mediating binary fate decisions in the M lineage. Not only are these genes potential SMA-9 targets, but determining how they function in the M lineage may also reveal additional molecular mechanisms in mesodermal patterning and cell fate specification. Together results from the proposed studies will expand our current understanding of how a complex lineage is built.7. Public Health Relevance: The mesodermal germ layer gives rise to a variety of functionally important cell types, including different muscle and non-muscle cells. Elucidating how different mesodermal cell fates are specified is not only important to the understanding of early stages of animal development, but will also guide investigations into the molecular basis of various cancers and genetic diseases that specifically affect mesodermally derived cell types.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM066953-08
Application #
7771717
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2002-09-02
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
8
Fiscal Year
2010
Total Cost
$312,498
Indirect Cost
Name
Cornell University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Shen, Qinfang; Shi, Herong; Tian, Chenxi et al. (2017) The C. elegans Spalt-like protein SEM-4 functions through the SoxC transcription factor SEM-2 to promote a proliferative blast cell fate in the postembryonic mesoderm. Dev Biol 429:335-342
Liu, Zhiyu; Shi, Herong; Szymczak, Lindsey C et al. (2015) Promotion of bone morphogenetic protein signaling by tetraspanins and glycosphingolipids. PLoS Genet 11:e1005221
Hale, Jared J; Amin, Nirav M; George, Carolyn et al. (2014) A role of the LIN-12/Notch signaling pathway in diversifying the non-striated egg-laying muscles in C. elegans. Dev Biol 389:137-48
Tian, Chenxi; Liu, Jun (2013) Repulsive guidance molecules (RGMs) and neogenin in bone morphogenetic protein (BMP) signaling. Mol Reprod Dev 80:700-17
Tian, Chenxi; Shi, Herong; Xiong, Shan et al. (2013) The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans. Development 140:4070-80
Krause, Michael; Liu, Jun (2012) Somatic muscle specification during embryonic and post-embryonic development in the nematode C. elegans. Wiley Interdiscip Rev Dev Biol 1:203-14
Barkan, Rachel; Zahand, Adam J; Sharabi, Kfir et al. (2012) Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis. Mol Biol Cell 23:543-52
Tian, Chenxi; Shi, Herong; Colledge, Clark et al. (2011) The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm. Development 138:1033-43
Amin, Nirav M; Shi, Herong; Liu, Jun (2010) The FoxF/FoxC factor LET-381 directly regulates both cell fate specification and cell differentiation in C. elegans mesoderm development. Development 137:1451-60
Tian, Chenxi; Sen, Debjeet; Shi, Herong et al. (2010) The RGM protein DRAG-1 positively regulates a BMP-like signaling pathway in Caenorhabditis elegans. Development 137:2375-84

Showing the most recent 10 out of 22 publications